PMID- 35081536 OWN - NLM STAT- MEDLINE DCOM- 20220517 LR - 20220531 IS - 1423-0143 (Electronic) IS - 1420-4096 (Linking) VI - 47 IP - 5 DP - 2022 TI - Mechanism of miRNA-141-3p in Calcium Oxalate-Induced Renal Tubular Epithelial Cell Injury via NLRP3-Mediated Pyroptosis. PG - 300-308 LID - 10.1159/000521795 [doi] AB - BACKGROUND/AIMS: Renal calculi represent a prevalent disorder associated with mineral deposition in renal calyces and the pelvis. Aberrant microRNA (miRNA) expression is implicated in renal injury. This study investigated the mechanism of miR-141-3p in calcium oxalate (CaOx) crystal-induced renal tubular epithelial cell (RTEC) injury. METHODS: Human RTECs HK-2 cells were treated with CaOx crystals to induce RTEC injury. Cell viability was evaluated using Cell Counting Kit-8 assay, and apoptosis was measured using flow cytometry. The contents of lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), interleukin (IL)-1beta, and IL-18 were measured using enzyme-linked immunosorbent assay kits. The expressions of NLRP3, cleaved caspase-1, and GSDMD-N were detected using Western blot. miR-141-3p and NLRP3 expressions were determined using reverse transcription quantitative polymerase chain reaction. The binding of miR-141-3p and NLRP3 was validated using a dual-luciferase assay. The role of NLRP3 in the protection of miR-141-3p on RTEC injury was verified using functional rescue experiments. RESULTS: CaOx crystals induced RTEC injury, manifested as attenuated cell viability, enhanced apoptosis, elevated intracellular LDH and MDA levels, and decreased SOD level. Pyroptosis of RTECs was enhanced by CaOx crystal induction, evidenced by elevated expressions of cleaved caspase-1, GSDMD-N, IL-1beta, and IL-18. miR-141-3p expression was reduced in CaOx crystal-induced RTECs. miR-141-3p overexpression alleviated CaOx crystal-induced RTEC injury and suppressed pyroptosis of RTECs. miR-141-3p bound to NLRP3 and thereby repressed NLRP3 expression. NLRP3 overexpression reversed the protective effect of miR-141-3p overexpression on RTECs. CONCLUSION: miR-141-3p repressed NLRP3-mediated pyroptosis by suppressing NLRP3 expression, thus protecting CaOx crystal-induced RTEC injury. CI - (c) 2022 The Author(s). Published by S. Karger AG, Basel. FAU - Gan, Xiu-Guo AU - Gan XG AD - Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Wang, Zhi-Hao AU - Wang ZH AD - Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, China. FAU - Xu, Hai-Tao AU - Xu HT AD - Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, China. LA - eng PT - Journal Article DEP - 20220126 PL - Switzerland TA - Kidney Blood Press Res JT - Kidney & blood pressure research JID - 9610505 RN - 0 (Interleukin-18) RN - 0 (MIRN141 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (NLRP3 protein, human) RN - 2612HC57YE (Calcium Oxalate) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 3.4.22.36 (Caspase 1) SB - IM MH - *Calcium Oxalate/metabolism MH - Caspase 1/metabolism MH - Epithelial Cells/metabolism/pathology MH - Humans MH - Interleukin-18/metabolism MH - *Kidney Calculi/metabolism/pathology MH - Male MH - *MicroRNAs/metabolism MH - *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Pyroptosis MH - Superoxide Dismutase/metabolism OTO - NOTNLM OT - Calcium oxalate OT - Pyroptosis OT - Renal calculi OT - Renal tubular epithelial cells OT - miR-141-3p EDAT- 2022/01/27 06:00 MHDA- 2022/05/18 06:00 CRDT- 2022/01/26 20:07 PHST- 2021/10/13 00:00 [received] PHST- 2022/01/04 00:00 [accepted] PHST- 2022/01/27 06:00 [pubmed] PHST- 2022/05/18 06:00 [medline] PHST- 2022/01/26 20:07 [entrez] AID - 000521795 [pii] AID - 10.1159/000521795 [doi] PST - ppublish SO - Kidney Blood Press Res. 2022;47(5):300-308. doi: 10.1159/000521795. Epub 2022 Jan 26.